Background: OS is the gold standard in measuring treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data and, therefore, surrogate endpoints are often used instead. Meta-analyses have been widely used for validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology and examined the extent of correlation between surrogate endpoints and OS for different cancer types.
Methods: A search was conducted in Oct 2010 to compile available published evidence in the English language for validation of disease progression-related endpoints as surrogates of OS based on meta-analyses. Extensive efforts were made to follow citations, and data was extracted by tumour type in metastatic disease.
Results: Published meta-analyses (N=26) were identified covering 6 advanced solid tumour types. Results that quantified the correlation between progression-free survival (PFS) and OS are shown in Table 1. In non-small cell lung cancer, 3 meta-analyses reported on response rate or time to progression but not PFS. One publication in head & neck cancer reported strong correlation between event-free survival and OS in multiple settings. One abstract in renal cell cancer presented a meta-analysis showing correlation (0.69) between effects on PFS and OS based on 21 trials.
Conclusions: PFS is the most commonly used surrogate measure in studies of advanced solid tumours, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and availability of second/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on PFS and OS in additional tumour types.
